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01-05-2009 | Laboratory Investigation - Human/Animal Tissue

Investigation of immunosuppressive mechanisms in a mouse glioma model

Authors: Alexander Ksendzovsky, Douglas Feinstein, Ryan Zengou, Anthony Sharp, Paul Polak, Terry Lichtor, Roberta P. Glick

Published in: Journal of Neuro-Oncology | Issue 1/2009

Abstract

The development of an immune competent mouse model for the study of immunosuppressive mechanisms is important for improving the efficacy of brain tumor immunotherapy. In the present study we investigated regulatory T cells (Tregs), TGF-β1 and other putative immunosuppressive cytokines using GL261 mouse glioma in C57BL mice. We explored whether tumor growth factor-beta1 (TGF-β1) is expressed and secreted by glioma cells constitutively or in response to a T-cell mediated immunity (simulated by conditioned media from T cells (TCM) activated by anti-CD3 antibody). We also investigated TGF-β1’s role in Treg mediated immunosuppression by quantifying TGF-β1secretion from T regulatory cells (Tregs) co-incubated with GL261 cells as compared to Tregs alone. Finally, we studied other newly identified cytokines that were secreted preferentially by glioma cells in response to CD3 activated TCM versus cytokines secreted by glioma cells in absence of T-cell activation (naïve TCM). TGF-β1expression was studied using RT-PCR and secretion was quantified using ELISA. A 308 protein cytokine array was used to identify and quantify cytokine expression. TGF-β1expression and secretion from glioma cells was found to be up-regulated by conditioned media from CD3-activated T cells, suggesting that this immunosuppressive cytokine is not secreted constitutively but in response to immunity. TGF-β1 was not found to be differentially secreted by Tregs co-incubated with glioma cells as compared to Tregs alone. This data suggest that TGF-β1immunosupppression may not be a Treg dependent mechanism in this glioma model. Finally, the cytokine array elucidated several other cytokines which were up-regulated or down-regulated by CD3-activated TCM. These results have several implications for enhancing immunotherapy treatment, including the potential benefit of TGF-β1inhibition in conjunction with immunotherapy, as well as the illumination of several other potential cytokine targets to be explored as shown by the cytokine array.

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Title: Investigation of immunosuppressive mechanisms in a mouse glioma model
Authors: Alexander Ksendzovsky
Douglas Feinstein
Ryan Zengou
Anthony Sharp
Paul Polak
Terry Lichtor
Roberta P. Glick
Publication date: 01-05-2009
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2009
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-009-9884-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Investigation of immunosuppressive mechanisms in a mouse glioma model

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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